脂肪间充质干细胞促进胰腺癌细胞增殖与侵袭的实验研究

Regulation effect of adipose-derived mesenchymal stem cells on pancreatic cancer cells

目的探讨脂肪间充质千细胞（ADSCs）对胰腺癌细胞增殖、侵袭的影响及其机制。方法从腹腔脂肪分离纯化培养ADSCs，建立胰腺癌细胞（SW1990细胞株与PANC-1细胞株）与ADSCs的双层培养体系。CCK一8比色法检测ADSCs对胰腺癌细胞增殖的影响，ELISA法测定培养液中基质细胞衍生性因子1（SDF-1）的浓度；评估SDF-1对胰腺癌细胞增殖的影响、AMD3100对ADSCs与胰腺癌细胞共培养的影响；体内实验观察ADSCs对胰腺癌细胞移植瘤生长的影响。结果ADSCs可促进胰腺癌细胞的增殖与侵袭（增殖：SW1990：1．535±0．153；PANC．1：1．370±0．100；对照组设为1；侵袭：SW1990：47．0±2．6比28．3±1．3；PANC—1：40．3±1．8比24．3±1．3；t=4．332～9．558，P〈0．05）。SDF一1在ADSCs中高表达而在胰腺癌细胞几乎不表达。SDF-1对胰腺癌的促增殖作用呈浓度依赖性。AMD3100能降低ADSCs对胰腺癌活性的影响。ADSCs促进了裸鼠SW1990细胞株种植瘤的生长[种植后第5周体积（1295±102）mm^3比（967±81）mm^3，t=5．614，P〈0．05]，但对PANC-1细胞株种植瘤的生长无促进作用。结论ADSCs具有促进胰腺癌细胞增殖、侵袭的潜能，其机制可能与SDF-1／CXCR4轴有关。

Objective To analyze the effects of adipose tissue-derived stem cells （ADSCs） on the proliferation and invasion of pancreatic cancer （ PaCa ） cells and the the possible mechanism involved. Methods ADSCs were isolated and co-cultured with PaCa cells. CCK-8 assay was used to detect the proliferation of PaCa ceils. An ELISA was used to determine the concentration of stromal cell-derived factor-1 （SDF-1） in the supernatants. The proliferation of PaCa cells by SDF-1 was measured. AMD3100 regulated the co-culture of ADSCs and PaCa. The tumor growth of PaCa cells was assessed after treatment by ADSCs in vivo. Results ADSCs can promote the proliferation and invasion of PaCa cells （proliferation： SW1990： 1. 535 ＋0. 153; PANC-1 ： 1. 370 ±0. 100; the value of control was 1 ; invasion： SW1990： 47. 0 ±2. 6 vs. 28.3 ± 1.3 ; PANC-1 ： 40. 3 ± 1.8 vs. 24. 3 ± 1.3 ; t = 4. 332 - 9. 558, P 〈 0. 05 ）. The expression of SDF-1 was high in ADSCs, but not in PaCa cells（69 ±5 vs. 0 and 0, F =389. 134, P 〈0. 01 ）. The promotion of SDF-1 on PaCa cells depends on the concentration. AMD3100 significantly downregulates these growth- promoting effects of ADSCs on PaCa cells. ADSCs significantly promoted the growth of SW1990 in nude mice at the 5＇h week （ volume： （ 1295 ± 102） mm3 vs. （967 ± 81 ） turn3, t = 5. 614, P 〈 0. 05 ）, but not in PANC-1 cell. Conclusion ADSCs can promote the proliferation and invasion of PaCa cells, which may involve the SDF-1/CXCR4 axis.